Approximately 34% of the adult population in the United States is overweight. Several investigators have postulated that the difficulty to maintain weight loss is linked to changes in skeletal muscle metabolism with weight perturbations. We are investigating this hypothesis by measuring the basal phosphate content and the in vivo oxidative capacity based on the PCr resynthesis rate (kPCr) after larger weight alterations in both obese and non-obese. Initial analysis of MRS measurements shows that a reduction in body weight is associated with an increase in the Pi content. In both the obese and non-obese a 10% decrease in body weight was associated with a 16% and 12% increase in basal Pi content respectively. Conversely, a 10% increase in body weight in the non-obese resulted in a 6% decrease in Pi content. The k Pcr(s-1) in the control group was shown to increase with weight. The skeletal muscle of the control group becomes more efficient at increased weight, and less efficient at lower weights. The obese group showed different changes in skeletal muscle capacity due to weight loss. The k Pcr at -20% was 2.45 as compared to 1.99 at baseline. The value at -10% was unchanged from baseline at 1.95. This suggests that in the obese population a decrease in weight was accompanied by an increase in the skeletal muscle oxidative capacity. Both the changes in kPCr and basal Pi content in the obese group support the hypothesis that weight perturbations affect skeletal muscle metabolism, with an increase in the oxidative capacity with weight loss and a decrease in oxidative capacity with weight gain. Analysis of basal Pi in the control group showed the same trend as the obese group, but k PCr measurements did not agree. Confirmative studies using in vitro biochemical measures of muscle biopsies and whole body oxygen consumption measurements during low level exercise are currently being performed. These data provide evidence that metabolic alterations may contribute to the high recidivism of weight increase after weight loss. Future studies will focus on using a spectra localization technique to look more specifically at the medial gastrocnemius at the different stages of weight loss and gain. Localized baseline measurements have been performed on one subject to date.